PYROGENIC DOSES OF INTRACEREBROVENTRICULAR INTERLEUKIN-1 DID NOT INDUCE ANALGESIA IN THE RAT HOT-PLATE OR COLD-WATER TAIL-FLICK TESTS

There are a few reports in the literature that cytokines can induce analgesia (5, 6, 18). The present study sought to characterize the analgesic effects of intracerebroyentricularly (icv) administered interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) in rats. In the cold-water tail-flick test (CWT), latency to tail withdrawal from a -3-degrees-C liquid was timed; in the hot-plate test (HP), latency to a rear paw lick or a jump from a 55-degrees-C surface was measured. In some experiments, core body temperature was also monitored with a rectal thermistor. In the CWT, human recombinant (hr) IFN-alpha induced a small, statistically significant effect at just one dose (15,000 U icv), but no dose of hr-IL-1alpha (250-1000 U icv) or hr-IL-1beta (125-2000 U icv) induced a significant effect at any time point. On the other hand, dose-related increases in body temperature were observed after icv injection of both IL-1alpha and IL-1beta. The largest hyperthermic effect was a 1.7 (+/-0.15) degrees-C rise 120 min after administration of 1000 U IL-1beta. In a second analgesic assay, the HP, IL-1beta was ineffective as well. Since IL-1 alone did not induce analgesia, we tested its capacity to potentiate morphine analgesia. Morphine (5.0 and 10 mug, icv) induced analgesia in the CWT (32.7 and 61.8 % maximum analgesia, respectively); however, there was no significant effect of IL-1beta on morphine-induced analgesia. In summary, we failed to find an analgesic effect of IL-1, alone or in combination with morphine, at doses which clearly had a physiological effect; this is in contrast to the reports cited above.